Pathology International 1997; 47: 65-57

Letter to the Editor Vascular intimal carcinomatosis: An autopsy case of unusual form of pulmonary metastasis of transitional cell carcinoma

Hiroshi Kobayashi,' SadahiroTamashima: Junsho Shigeyama? Shin-ichi Shimizu' andTaizan Suchil Departments of Pathology and *Hematology, Seirei Hamamatsu General Hospital, Hamamatsu and Department of Medicine, Kosai Municipal Hospital, Kosai, Japan

A 44-year-old woman wlth an unusual form of pulmonary metastasls Is descrlbed. She presented wlth pulmonary thrombosis and cllnlcal signs of dissemlnated intravascular coagulatlon (DIC) and died of cerebral hemorrhage. The autopsy study revealed transitlonal cell carcinoma of the left renal pehrls with pulmonary thrombosis In the large arteries. The lntima of the vessels were intact on gross lnspectlon except where the thrombi adhered to.The thrombi Contained no tumor cells. However, microscopic examination identffled that the metastatic carcinoma diffusely replaced the endothelium and proliferated on to the lntimal surface without lnvaslon of the wall and metastatic nodules In the parenchyma. Other examined organs had neither primary nor metastatic tumors, except for microscopic metastasis to the inferior vena cava.To date, this pattern of metastasls has not been noted In previous literature. This condition was deslgnated as being vascular intlmal carclnomatosis because of its characteristic manner of tumor prollferation on vascular Intima.

Key words: pulmonary metastasis, pulmonary thrombosis, transitional cell carcinoma, vascular intimal carcinornatosis

The lung is a common site for metastasis of malignant tumors. Various patterns of metastasis are truly recognized and widely discussed.'n2 We report an unusual case of transitional cell carcinoma of renal pelvic origin metastasizing to the main pulmonary arteries. Their large branches diffusely replaced the endothelium of these vessels without invasion and tumor emboli, and consequently caused pulmonary thrombosis with a clinical manifestation of disseminated intravascular coagulation (DIC).

The patient, a 44-year-old woman, complained of nasal bleeds, gingival hemorrhage, and skin purpura. She was admitted to hospital on 6 December 1994. Prothrombin time

Correspondence: Hiroshi Kobayashi, MD, Department of Pathology, Seirei Hamamatsu General Hospital, 2-12-1 2 Sumiyoshi, Hamamatsu 430, Japan.

Received 1 January 1997. Revised manuscript accepted for publication 2April199i'.

and activated partial thromboplastin time were prolonged with 20.4 and 51.6 s, respectively. A decrease in fibrinogen (29 mg/dL) and an increase in fibrin degeneration product (>lo0 kg) were identified. Peripheral blood and bone marrow smears were normal. The patient was diagnosed as having DIC, possibly due to a malignancy because of high levels of CA19-9 and CAI 25 (1 47 and 123 UlmL, respectively). Although a systemic examination for malignancy was conducted, no tumors were detected. While the hemorrhagic tendency had tended to ameliorate, chest pain with bilateral hemorrhagic effusions suddenly appeared on 13 December. At this time a chest computerized tomographic scan pinned down pulmonary thrombosis without any thrombi in the deep veins of the extremities. On the suspicion of pulmonary vasculitis, probably located in the large arteries, methyl- prednisolone and dexamethasone were administered, but treatment was unsuccessful. On 22 February 1995. the patient suffered from massive nasal bleeding and hematemesis and died of cerebral hemorrhage the next morning.

An autopsy was performed 2 h after the patient's death. The left kidney weighed 160 g and had several infarcts on its surface. The cut-section revealed many low-papillary tumors on the pelvic mucosa with focal invasion to the papilla forming a white tumor 1 cm in size. Histologically. the tumors were transitional cell carcinoma, Grade I I , with a relatively wide area of grade I and prominent involvement of the renal veins. No tumor emboli were observed in the main renal vein and inferior vena cava. Other examined organs contained no grossly visible tumors.

The weight of the left and right lung was 210 and 370 g, respectively. The middle right and lower lobe had hemorrhagic infarcts measuring 4x5 and 10x8 cm, respectively. Thrombi were present in both main pulmonary arteries and the segmental branches. Grossly, intimal surfaces of these arteries were intact except where the thrombi had adhered (Fig. 1). However, when the arteries were checked on microscopic slides, the transitional cell

656 H. Kobayashi era/.

carcinoma had massively proliferated on the intima the way the carcinoma cells diffusely replaced the endothelium (Fig. 2). Although the intima had partly thickened with fibrous tissue, the tumor cells were confined to the intimal surface

without invasion. This change was seen in the main pulmonary arteries up to 300 pm in diameter (Fig. 3). lmmunohistochemically, the tumor cells were stained for cytokeratin but were negative for factor VIII-related antigen and vimentin.

The thrombi, which consisted solely of fibrin and erythrocyte, adhered to and grew on the intima that were free from the intimal lining of the tumor. Arteries smaller than 300 pm showed neither tumor emboli nor tumor proliferation on the intima. Tumor proliferation on the intima was also observed in a part of the inferior vena cava, but not in the right atrium, right ventricle, nor pulmonary trunk. No microscopic metastases were identified in any organs examined, except for the pulmonary arteries and inferior vena cava.

In general, pulmonary metastases are brought about via blood and lymphatic vessels and through direct invasion. With regard to hematogenous metastasis, multiple and bilateral tumors of various sizes are often formed.’.* Vascular tumor emboli sometimes predominate in their mode of metastasis. They usually occur in small vesselsw and rarely in vessels larger than segmental b ranche~ .~ 6 7 In the present case, the tumor metastasizing to the pulmonary arteries

Figure 1 surfaces except where the thrombus has adhered.

A pulmonary artery. which grossly shows the intact intimal

Figure 2 Microscopic photograph of the pulmonary arteryof Fig 1, which shows diffuse proliferation of the tumor on the intima (upper field) and normal lung parenchyma (lower field)

Figure 3 A medium-sized artery was lined with transitional epithelium (lower field) and a bronchus with ciliated epithelium (upper field)

Unusual spread of transitional cell carcinoma 657

larger than 300 pm in diameter diffusely replaced the endothelium and proliferated exclusively on to the intimal surface without any invasion and tumor emboli. This explains why the microscopic pictures taken of the arteries looked as if they were ureters. To date, it seems that a case such as this has not been reported. We would like to designate the lesion as being vascular intimal carcinomatosis because of its unique manner of tumor proliferation on vascular intima. Although this condition may be rare, studies of similar cases and further definition for this condition may shed some light upon the complicated mechanism of tumor metastasis.

ACKNOWLEDGMENTS

We are grateful to Mrs Fumiko Sakata, Mrs Yurika Sawaki, and Mr Makoto Yamada for their technical assistance. We thank Mr Masami Totsuka and Mr Hisanori Suzuki for their assistance in preparing the photographs.

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